Abstract
Hepatic ischemia-reperfusion injury is a dynamic process consisting of two stages: ischemia and reperfusion, and triggers a cascade of physiological and biochemical events. Given the important role of microRNAs in regulating gene expression, we analyzed gene expression changes in mouse livers at sham control, ischemia stage, and reperfusion stage. We generated global expression profiles of microRNA and mRNA genes in mouse livers subjected to ischemia-reperfusion injury at the three stages, respectively. Comparison analysis showed that reperfusion injury had a distinct expression profile whereas the ischemia sample and the sham control were clustered together. Consistently, there are 69 differentially expressed microRNAs between the reperfusion sample and the sham control whereas 28 differentially expressed microRNAs between the ischemia sample and the sham control. We further identified two modes of microRNA expression changes in ischemia-reperfusion injury. Functional analysis of both the differentially expressed microRNAs in the two modes and their target mRNAs revealed that ischemia injury impaired mitochondrial function, nutrient consumption, and metabolism process. In contrast, reperfusion injury led to severe tissue inflammation that is predominantly an innate-immune response in the ischemia-reperfusion process. Our staged analysis of gene expression profiles provides new insights into regulatory mechanisms of microRNAs in mouse hepatic IR injury.
Highlights
There is severe shortage of donor livers per year [1]
We profiled expression of both microRNAs and mRNAs in the mouse livers subjected to sham operation, warm ischemia (WI), and ischemia followed by reperfusion (IR), respectively
The mice were randomly divided into three groups of six mice each: (i) the sham group underwent a sham operation without vascular occultation; (ii) the warm ischemia (WI) group with hepatic vascular occultation for 90 min; and (iii) the ischemia followed by reperfusion (IR) group underwent vascular occultation for 90 min followed by 120 min of hepatic reperfusion
Summary
There is severe shortage of donor livers per year [1]. The organ shortage has turned to the use of extended criteria donor livers including donor livers having been subjected to prolonged storage as well as from non-heart-beating donors. The common feature of these “marginal” donor livers is high susceptibility to ischemia-reperfusion injury. MiRNA Expression Profiling in Mouse Liver IRI injury may increase the early organ failure and the incidence of rejection after transplantation [2]. The survival rate of these “marginal” livers after transplantation is lower than the normal criteria donor livers. Fully understanding the molecular mechanism of hepatic ischemia-reperfusion injury would promote the use of these “marginal” donor livers in clinical surgeries
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